Many forms of intrauterine growth retardation (IUGR) are likely to be the end result of a fetal metabolic adaptation to an imbalance between supply and demand of metabolic substrates. Recent studies in our ovine heat- stress model of placental insufficiency induced fetal growth retardation (PI-IUGR model) confirm our hypothesis that the marked IUGR characteristic to this model is associated with a placental transport limitation of multiple substrates, a metabolic adaptation which is different from that observed in other IUGR models. Our current hypotheses are that placental insufficiency occurs early in gestation in the PI-IUGR model and that the resulting placental amino acid transport limitation can be compensated for by long-term continuous maternal amino acid supplementation. The studies utilize our recently developed techniques of transabdominal ovine fetal ultrasonography to measure fetal growth in utero and our recently developed leucine two-tracer study design to compare the metabolism of this essential amino acid in the PI-IUGR fetus and placenta with the normal fetus by infusing L-[1-/14C]leucine into the fetus and L-[1- /13C]leucine is into the ewe. Specific aim 1 tests the hypothesis that decreased food intake does not contribute to IUGR of the PI-IUGR fetus. Specific aim 2 tests the hypothesis that placental insufficiency in the PI-IUGR model is irreversible by 0.6 term. Specific aims 3 and 4 test the hypothesis that leucine accretion by the PI-IUGR fetus and placenta will not increase after a 4-hour maternal amino acid infusion but will increase after a 30 day maternal amino acid infusion. Such studies provide an understanding of adaptative metabolic strategies in the IUGR fetus.